Lymphoma
Conditions
Keywords
contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
Brief summary
RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Colony-stimulating factors such as GM-CSF increase the number of immune cells found in bone marrow and peripheral blood. It is not yet known whether combining rituximab and GM-CSF with vaccine therapy may cause a stronger immune response and kill more cancer cells. PURPOSE: This randomized phase III trial is studying giving rituximab and GM-CSF together with vaccine therapy and comparing it to giving rituximab and GM-CSF alone in treating patients with newly diagnosed, relapsed, or refractory B-cell non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES: Primary * Compare time to disease progression in patients with grade 1, 2, or 3 follicular B-cell non-Hodgkin's lymphoma who respond (i.e., complete or partial response, or stable disease) to treatment with rituximab and are then treated with sargramostim (GM-CSF) with vs without autologous immunoglobulin idiotype-KLH conjugate vaccine. Secondary * Compare response rate improvement in patients treated with these regimens. * Compare overall complete response rate in patients treated with these regimens. * Compare duration of response in patients treated with these regimens. * Determine the safety of these regimens in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior treatment (yes vs no) and response to rituximab during study (complete response \[CR\] or partial response \[PR\] vs stable disease \[SD\]). All patients receive rituximab IV once weekly for 4 weeks. Five weeks after the last dose of rituximab, patients are assessed for response. Patients with progressive disease are removed from the study and do not undergo randomization. Patients with a CR, PR, or SD are randomized to 1 of 2 treatment arms. * Arm I: Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine subcutaneously (SC) on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4. * Arm II: Patients receive placebo SC on day 1. Patients also receive GM-CSF SC on days 1-4. In both arms, treatment repeats monthly for 6 months in the absence of unacceptable toxicity or clinically significant progressive disease. After the first 6 months, patients with a CR, PR, or SD may continue to receive treatment (per treatment arm as above) every 2 months for 1 year (total of 6 doses) and then every 3 months thereafter in the absence of disease progression. Patients are followed every 3 months for 2 years and then every 6 months until disease progression. PROJECTED ACCRUAL: A total of 342 evaluable patients (171 per treatment arm) will be accrued for this study within 18 months.
Interventions
BIOLOGICALrituximab
BIOLOGICALsargramostim
Sponsors
Favrille
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL) * Grade 1, 2, or 3 * Meets 1 of the following criteria for treatment with rituximab: * Treatment naïve * Relapsed or refractory disease after prior chemotherapy * Relapsed after a prior documented response (i.e., complete or partial response) to rituximab of at least 6 months duration * Tumor accessible for biopsy OR existing biopsy material (taken within the past 6 months) suitable for vaccine preparation * Measurable or evaluable disease after tumor tissue procurement for vaccine production * No more than 2 prior treatment regimens for NHL * Single regimens include any of the following: * Maintenance rituximab * Rituximab administered once weekly for 8 courses * Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab\* NOTE: \*CHOP followed by rituximab at time of relapse is considered 2 treatment regimens * No history of CNS lymphoma or meningeal lymphomatosis PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute granulocyte count ≥ 1,500/mm\^3 * Platelet count ≥ 75,000/mm\^3 (unless related to bone marrow involvement by lymphoma) * Hemoglobin ≥ 10g/dL Hepatic * Not specified Renal * Not specified Cardiovascular * No congestive heart failure Pulmonary * No compromised pulmonary function Immunologic * HIV negative * No prior allergic response to GM-CSF * No active bacterial, viral, or fungal infection Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No psychiatric disorder that would preclude study participation * No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No other serious nonmalignant disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * See Chemotherapy * At least 4 weeks since prior immunotherapy * No prior radiolabeled anti-lymphoma antibody (e.g., iodine I 131 tositumomab or ibritumomab tiuxetan) * No prior autologous or allogeneic stem cell transplantation * No prior lymphoma-specific idiotype immunotherapy (e.g., Id vaccine) * No prior investigational vaccine or immunotherapeutic containing keyhole limpet hemocyanin (KLH) Chemotherapy * See Disease Characteristics * At least 4 weeks since prior chemotherapy * More than 9 months since prior fludarabine * More than 2 years since prior chemotherapy/rituximab combination therapy (e.g., CHOP/rituximab or cyclophosphamide, vincristine, and prednisone \[CVP\]/rituximab) * No more than 6 total prior treatment courses with fludarabine Endocrine therapy * No concurrent steroids for allergic reaction to sargramostim (GM-CSF) Radiotherapy * See Biologic therapy * At least 4 weeks since prior radiotherapy Surgery * Not specified Other * At least 4 weeks since prior experimental therapy * No concurrent systemic immunosuppressive therapy * No other concurrent anti-lymphoma therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to progression after 248 patients have progressed | — |
Secondary
| Measure | Time frame |
|---|---|
| Response rate improvement after 248 patients have progressed | — |
| Overall complete response rate by modified Cheson Criteria after 248 patients have progressed | — |
| Duration of response by modified Cheson Criteria after 248 patients have progressed | — |
| Safety by Common Toxicity Criteria (CTC) after 248 patients have progressed | — |
Countries
United States
Outcome results
None listed